Summary
Wilms tumor (nephroblastoma) is the most common renal malignancy in children, typically affecting children between 2 and 5 years of age. A minority of cases are associated with specific syndromes (e.g., WAGR, Beckwith-Wiedemann) and gene mutations (e.g., WT1). Wilms tumor is typically an incidental finding that manifests as a large abdominal mass. Other signs and symptoms may occur, such as hematuria and abdominal pain, especially in tumors that are large, ruptured, or metastasized. Treatment consists of tumor resection and chemotherapy for all stages (except for very low-risk tumors), while radiation is predominantly used in advanced disease.
Epidemiology
Etiology
The exact etiology of Wilms tumor remains unknown, but it is associated with several genetic mutations and syndromes.
Genetic predisposition [2][3]
- Gene mutations have been found in children both with and without genetic syndromes who have Wilms tumor.
- Associated with loss of function mutations of tumor supressor genes on chromosome 11
Associated syndromes [5]
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WAGR syndrome: Deletion of the 11p13 band leads to the deletion of the WT1 gene and other genes, such as PAX6. [6]
- Wilms tumor
- Aniridia
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Genitourinary anomalies
- Pseudohermaphroditism, undescended testes in males (due to gonadal dysgenesis)
- Early-onset nephrotic syndrome
- Range of intellectual disability
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Denys-Drash syndrome: point mutation in WT1 gene, which encodes a zinc finger transcription factor [7]
- Wilms tumor
- Pseudohermaphroditism, undescended testes in males (due to gonadal dysgenesis)
- Early-onset nephrotic syndrome caused by diffuse mesangial sclerosis
- Beckwith-Wiedemann syndrome: mutations of the WT2 gene
WAGR syndrome consists of Wilms tumor, Aniridia, Genitourinary anomalies, and Range of intellectual disability.
Denys-Drash syndrome is a mild form of WAGR without aniridia or intellectual disability.
Clinical features
Abdominal symptoms
-
Palpable abdominal mass (often found incidentally)
- Non-tender
- Unilateral and large but not crossing midline
- Smooth and firm
- Abdominal pain (∼ 40% of cases)
Other signs and symptoms
- Hematuria (∼ 25% of cases)
- Hypertension (∼ 25% of cases)
- In cases of subcapsular hemorrhage:
- Symptoms caused by metastatic spread (e.g., pulmonary symptoms)
Wilms tumor should be suspected in a toddler with a non-tender abdominal mass, especially if it is firm, smooth, and associated with hematuria and/or hypertension.
Careless palpation of a Wilms tumor can result in rupture of the renal capsule and tumor spillage!
Stages
National Wilms Tumor Study (NWTS) system [8] | |||
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Stage | Tumor location | Tumor spread | Surgery |
I |
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II |
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III |
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IV |
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V |
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Diagnostics
- Urinalysis: hematuria may be present
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Imaging
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Ultrasound (best initial test)
- Hypervascular tumor
- Mostly uniform echogenicity with hypoechoic areas of necrosis
-
Abdominal CT/MRI
- To assess extent of involvement
- Surgical planning
- CT thorax/CXR
- To detect metastases
- Staging
-
Ultrasound (best initial test)
Biopsy is usually reserved for assessing nodules that are suspected metastases, as tumor capsule rupture and spillage results in more advanced staging and intensive treatment.
Pathology
Overview
- Wilms tumor consists of embryonic glomerular structures.
- May include cysts, hemorrhage, or necrosis
- Typically has a pseudocapsule
Histology
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Classic type: consists of three cell types
- Epithelial cells (i.e., glomeruli and tubules)
- Stromal cells
- Undifferentiated blastemal cells of metanephric origin
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Anaplastic type
- Contains multipolar polypoid mitotic figures
- Marked hyperchromasia of nuclei
Differential diagnoses
Neuroblastoma
Differential diagnosis of Wilms tumor and neuroblastoma [9] | ||
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Wilms tumor | Neuroblastoma | |
Clinical findings (e.g., fever, weight loss) |
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CT/MRI findings (e.g., calcifications, vascular encasement, midline crossing) |
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I-123 MIBG scan |
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Catecholamine metabolites in urine (VMA, HVA) |
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Other renal tumors
- Clear cell sarcoma
- Rhabdoid tumor
- Congenital mesoblastic nephroma
- Renal cell carcinoma
- Renal medullary carcinoma
The differential diagnoses listed here are not exhaustive.
Treatment
Treatment of Wilms tumor according to stage | ||||
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Treatment | Stages I and II | Stages III and IV | Stage V (bilateral) | |
Surgery | Renal parenchymal-sparing resection |
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Nephrectomy |
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Chemotherapy | Preoperative chemotherapy |
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Doxorubicin |
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Dactinomycin and vincristine |
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Radiation |
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Prognosis
- Good prognosis: survival rates are > 90% [10]
- The majority of tumor recurrences happen within two years of treatment.
Prevention
- Regular screening of children with associated syndromes (e.g., abdominal ultrasound every three months until the age of 8)